C. trachomatis is a Gram-negative bacterium which is an obligate intracellular pathogen. It is a common cause of urogenital tract infections, which leads to pelvic inflammatory disease (10-20% of cases), infertility and ectopic pregnancy. Such conditions are common in industrialised countries and are caused by serovars D-K.
C. trachomatis is also a leading cause of ocular infections, resulting in trachoma (150 million cases annually) and blindness (6 million cases annually), mainly in developing countries. These conditions are caused by serovars A-C. Infection with serovars L1-L3 of C. trachomatis causes lymphogranuloma venereum.
Vaccine development has been identified as essential to controlling infection with C. trachomatis. Vaccines against C. trachomatis appear to depend on a Th1-polarized cell-mediated immune response, in particular on CD4+ lymphocytes that produce IFN-γ. For example, depletion of CD4+ T cells in mice results in loss of protective immunity [1], and adoptive transfer of Chlamydia-specific CD4+ T cells confers protection against challenge with C. trachomatis ([2],[3]). Furthermore, recent studies report that C. trachomatis infection in mice induces a CD4-Th1 protective immune response, indicating that critical Chlamydia antigens are processed and presented via the MHC class II pathway ([4];[5]).
Immune protection against infection with C. trachomatis is likely to be mediated by immunization with C. trachomatis proteins that are targets of CD4+ T cells and that are capable of inducing B-cell responses. B-cells and antibodies have been shown to be important for enhancing the protective effector T-cell response against primary infection [6]. B-cells and antibodies also play an important role in resolution of secondary infection ([7],[8]).
Neutralizing antibodies have been shown to play an important role in protection against Chlamydia infection.
Numerous studies on the most promising vaccine candidate (Major Outer Membrane Protein, MOMP) have shown that an effective vaccine is likely to be based on several C. trachomatis antigens. The homologue proteins CT823 of Chlamydia trachomatis (Ct) and TC0210 of Chlamydia muridarum (Cm) are annotated as serine proteases and share a 93.36 percent sequence identity. Previous studies, with mass spectrometric and cytofluorimetric analysis on CT823 have confirmed its localization on the surface of the bacterium[9]. The CT823 antigen is able to induce a specific CD4-Th1 response in splenocytes isolated from mice infected with C. trachomatis and has been predicted to contain MHC class II epitopes ([10];[11]).
10. It is an object of the invention to provide a vehicle for delivering antigens such as Chlamydia CT823 in vaccine formulations.